Safety Monitoring of mRNA COVID-19 Vaccine Third Doses Among Children Aged 6 Months–5 Years — United States, June 17, 2022–May 7, 2023

As of May 7, 2023, CDC's Advisory Committee on Immunization Practices (ACIP) recommends that all children aged 6 months-5 years receive at least 1 age-appropriate bivalent mRNA COVID-19 vaccine dose. Depending on their COVID-19 vaccination history and history of immunocompromise, these children might also need additional doses* (1-3). Initial vaccine safety findings after primary series vaccination among children aged 6 months-5 years showed that transient local and systemic reactions were common whereas series adverse events were rare (4). To characterize the safety of a third mRNA COVID-19 vaccine dose among children aged 6 months-5 years, CDC reviewed adverse events and health surveys reported to v-safe, a voluntary smartphone-based U.S. safety surveillance system established by CDC to monitor health after COVID-19 vaccination (https://vsafe.cdc.gov/en/) and the Vaccine Adverse Event Reporting System (VAERS), a U.S. passive vaccine safety surveillance system co-managed by CDC and the Food and Drug Administration (FDA) (https://vaers.hhs.gov/) (5). During June 17, 2022-May 7, 2023, approximately 495,576 children aged 6 months-4 years received a third dose (monovalent or bivalent) of Pfizer-BioNTech vaccine and 63,919 children aged 6 months-5 years received a third dose of Moderna vaccine.† A third mRNA COVID-19 vaccination was recorded for 2,969 children in v-safe; approximately 37.7% had no reported reactions, and among those for whom reactions were reported, most reactions were mild and transient. VAERS received 536 reports after a third dose of mRNA COVID-19 vaccine for children in these age groups; 98.5% of reports were nonserious and most (78.4%) were classified as a vaccination error.§ No new safety concerns were identified. Preliminary safety findings after a third dose of COVID-19 vaccine for children aged 6 months-5 years are similar to those after other doses. Health care providers can counsel parents and guardians of young children that most reactions reported after vaccination with Pfizer-BioNTech or Moderna vaccine were mild and transient and that serious adverse events are rare.

were identified. Preliminary safety findings after a third dose of COVID-19 vaccine for children aged 6 months-5 years are similar to those after other doses. Health care providers can counsel parents and guardians of young children that most reactions reported after vaccination with Pfizer-BioNTech or Moderna vaccine were mild and transient and that serious adverse events are rare.
Starting June 19, 2022, parents could enroll children aged 6 months-4 years in v-safe after mRNA COVID-19 vaccination. ¶ A parent with a v-safe account could register a child or adolescent aged <16 years, receive text message reminders, and complete health surveys on behalf of the child.** Health surveys sent daily during the week after vaccination inquire about local injection site and systemic reactions and health impacts; respondents can provide additional information via free-text responses. CDC's v-safe call center contacts registrants who report receiving medical care to request more information; registrants are encouraged to complete a VAERS report, if indicated.
VAERS accepts reports of postvaccination adverse events from health care providers, vaccine manufacturers, and members of the public. † † Signs, symptoms, and diagnoses reported to VAERS are assigned Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs) by VAERS staff members. § § This report includes data for children aged 6 months-5 years who received a third mRNA COVID-19 dose during ¶ On May 19, 2023, CDC closed enrollment in v-safe for COVID-19 vaccines.
Health check-ins (and follow-up calls, if needed) for any doses added before May 19 will continue until June 30, 2023. ** Health check-ins are sent via text messages that link to web-based surveys on days 0-7 after vaccination; then weekly through 6 weeks after vaccination; and then 3, 6, and 12 months after vaccination. Specific questions were included for children aged 6 months-2 years who might not be able to describe reactions or who might experience reactions that differ from those experienced by children aged ≥3 years. Parents use the following definitions to describe the severity of a child's symptoms: mild (noticeable, but not problematic), moderate (limit normal daily activities), or severe (make daily activities difficult or impossible). V-safe also sends text-message reminders when a person is eligible for their next vaccine dose; an additional reminder was sent on The most commonly reported reactions after receipt of either vaccine among children aged 6 months-2 years were irritability or crying, injection site pain, sleepiness, and fever (Table 2). Among children aged 3-5 years, the most frequently reported reactions were injection site pain, fatigue, and fever. Most reactions were described as mild in severity (noticeable, but not problematic). Parents of 211 (7.1%) children aged 6 months-5 years reported at least once during the week after vaccination that their child was unable to perform normal daily activities, including 126 Pfizer BioNTech recipients and 85 Moderna recipients (Table 1); 90 (3.0%) parents reported seeking medical care for their child. Among these, 61 (67.8%) reported that care was received in an outpatient clinic; one child was hospitalized for pneumonia; 43 (48.0%) had additional information available from the v-safe call center. Parents of 30 children indicated that medical care was unrelated to vaccination, 11 parents completed a VAERS report, and two parents indicated that the report was made in error. Symptoms or signs of infection (e.g., cough, conjunctivitis, or hand-foot-and-mouth disease rash) were reported via free text or VAERS report for 34 of the 90 reports of medical care.

Review of VAERS Data
During June 17, 2022-May 7, 2023, VAERS received and processed 407 reports of adverse events among children aged 6 months-4 years after receipt of Pfizer-BioNTech vaccine and 129 reports for children aged 6 months-5 years after Moderna vaccine (Table 3). § § § Most reports were for children who received COVID-19 vaccine without concomitantly administered vaccines (487; 90.9%).
The most common events reported (420; 78.4%) were vaccination errors (e.g., incorrect product formulation administered, inappropriate schedule of product administration, expired product administered, or incorrect dose administered). Among 330 reports of vaccination errors after administration of Pfizer-BioNTech and 90 after Moderna vaccines, 27 (5.0%) reports indicated that an adverse health event had occurred.
After the exclusion of reports specifying vaccination error, 108 nonserious reports remained, including 71 after Pfizer-BioNTech and 37 after Moderna vaccination. After review, the most commonly reported nonserious events included infection ¶ ¶ ¶ (57; 52.8%), no adverse event (13; 12.0%), and rash (nine; 8.3%). § § § Processed VAERS reports are those that have been coded using MedDRA, deduplicated, and undergone standard quality assurance and quality control review. ¶ ¶ ¶ Clinical review identified 57 reports of infection: cough or wheezing (three), COVID-19 (12), croup (three), ear infection (15), influenza (one), norovirus (one), pneumonia (one), respiratory tract infection (15), hand, foot, and mouth (one), strep throat (four), and viral rash (one).  . † Children whose parents reported a reaction or health impact at least once during days 0-7 postvaccination. Specific questions were included for children aged 6 months-2 years who might not be able to describe reactions or who might experience different reactions from those experienced by children aged ≥3 years. § Children whose parents or guardians reported neither injection site nor systemic reactions.
Eight (1.5%) serious reports were made to VAERS: six for children who received Pfizer-BioNTech and two for children who received Moderna. Clinical impressions of the serious reports included acute hemorrhagic edema of infancy (infection with non-SARS-CoV-2 coronavirus), diabetic ketoacidosis (following new onset of diabetes mellitus type 1), Henoch-Schönlein purpura, Kawasaki disease, new-onset afebrile seizure (two), pneumonia, and viral exacerbation of asthma. After review of all available information, no evidence suggested that these reported events were related to vaccination.

Discussion
This report provides findings from v-safe and VAERS for children aged 6 months-5 years who received a third dose of mRNA COVID-19 vaccine during June 17, 2022-May 7, 2023; during this period, approximately 559,495 third doses were administered to children in this age group. The findings in this report are consistent with those from postauthorization safety surveillance of the first 2 doses of mRNA COVID-19 vaccines. Systemic reactions after receipt of the first or second doses were more commonly reported for children aged 6 months-2 years than for those aged 3-5 years; 44.7% of VAERS reports included at least one vaccination error (4).
Reports to v-safe of injection site and systemic reactions after a third dose of mRNA COVID-19 vaccine were similar in frequency to those reported after a first (19.0%-32.4% reports of injection reaction and 32.2%-55.8% reports of systemic reaction) or second dose (18.3%-47.1% reports of injection

. Reactions most commonly reported to v-safe during days 0-7 postvaccination for children ages 6 months-5 years (N = 2,969)* who received a third dose of Pfizer-BioNTech or Moderna COVID-19 vaccine, by severity -United States, June 17, 2022-May 7, 2023
Reaction or health impact (age group) * Data were included for children aged 6 months-4 years who received a third Pfizer-BioNTech dose during June 17, 2022-May 7, 2023, and for children aged 6 months-5 years who received a third Moderna dose during June 17, 2022-May 7, 2023. † Children whose parents or guardians reported a reaction or health impact at least once during days 0-7 after vaccination. Includes the most severe event reported during the 0-7 window. Parents and guardians who participate in v-safe use the following definitions to describe the severity of a child's symptoms: mild (noticeable, but not problematic), moderate (limit normal daily activities), or severe (make daily activities difficult or impossible). § Fever is self-reported and registrants are not required to record a temperature. Among children who had a reported temperature and met the definition for fever reaction and 29.2%-58.2% reports of systemic reaction) among children aged 6 months-5 years (4). They were less frequent than those reported for children aged 5-11 years after a monovalent or bivalent booster dose (6,7). Approximately 38% of parents reported to v-safe that their child experienced no reactions in the week after a third mRNA vaccine dose. Most parents of children who received medical care reported that care was unrelated to vaccination. Many children who received medical care had signs and symptoms of an acute infection.

No. (%) reporting reaction or health impact after vaccination
After administration of approximately 550,000 third doses of mRNA COVID-19 vaccine to children aged 6 months-5 years, eight serious reports were received by VAERS. More than 98.0% of reports were nonserious; most represented vaccination errors (78.4%). Vaccination errors have constituted a large proportion of VAERS reports among children. For example, 85.0% of VAERS reports for children aged 5-11 years after bivalent booster vaccination were related to vaccination error (7). Among reports not specifying vaccination error, one half were of an unrelated infection. Recent ACIP recommendations simplifying guidance for bivalent vaccination might reduce reports of vaccination error (3).
The findings in this report are subject to at least four limitations. First, v-safe is a voluntary program; as a result, data might not be representative of the vaccinated population. Second, VAERS is a passive reporting system and is subject to reporting biases and underreporting, especially of nonserious events (5). Third, this report combined data for monovalent and bivalent mRNA COVID-19 vaccine formulations. However, findings among older children did not differ by formulation (7). Finally, interpretation of these data is limited by the short surveillance period and small denominator of vaccinated children aged 6 months-5 years.
All children aged 6 months-5 years are recommended to receive at least 1 bivalent dose and might need multiple COVID-19 vaccine doses depending on their age and COVID-19 vaccination history**** (3). No new safety findings were identified among **** As of May 7, 2023, monovalent COVID-19 vaccines are no longer authorized for use in the United States.

Summary
What is already known about this topic?
All children aged 6 months-5 years are recommended to receive ≥1 bivalent mRNA COVID-19 vaccine dose; approximately 550,000 children in these age groups have received a third monovalent or bivalent mRNA vaccine dose.
What is added by this report?
In v-safe, 38% of children had no reported reactions after a third dose; most reported reactions were mild and transient. Vaccination errors accounted for 78% of events reported to the Vaccine Adverse Event Reporting System.
What are the implications for public health practice?
Findings after receipt of a third mRNA vaccine dose among young children were similar to those described after receipt of 1 and 2 doses; no new safety concerns were identified.
children aged 6 months-5 years after receipt of a third dose. Most reported reactions after vaccination were mild and transient. Although SARS-CoV-2 infection among young children typically results in mild infection, it can result in serious illness, including multisystem inflammatory syndrome in children, long-term sequalae, and death (8). mRNA COVID-19 vaccination provides protection against symptomatic SARS-CoV-2 infection for at least 4 months after vaccination among children aged 3-5 years (9). CDC and FDA will continue to monitor vaccine safety and will provide updates to help guide COVID-19 vaccination recommendations.